Comparison of diagnostic accuracy of different peripheric parameters of thyroid function.

Diagnostic value of a scope of peripheric parameters of thyroid function was assessed in an unselected group of untreated patients with suspected thyroid disorder, further in untraeted selected patients (without cardiac involvement) and in treated patients. Comparison of relative values of individual tests was performed, based on relation to plasma thyroid hormone level represented by PBI. It was found that: 1. The diagnostic value of heart rate, plasma cholesterol level, B. M. R. and Hegglin's sign (T-2s interval) is of a very limited degree. 2. The diagnostic accuracy of AJT, Q-Kd interval and PEP was found to be of considerable interest even in unselected patients. Values of IRVD and D indices found for these tests are comparable and allow the immediate estimation of thyroid function in bedside diagnosis. 3. The diagnostic value of PEP could be enhanced by exclusion of patients with suspected or proved cardiac disorder or myocardial failure; this may be useful for physiologic studies. 4. While heart rate is profoundly and inconsistently influenced by beta-blockade, AJT is influenced to a minimal degree only and Q-Kd and PEP are uniformly shifted to higher values, allowing thus diagnostic evaluation during this form of treatment also. 5. As Q-Kd is considerably age-and height-dependent, AJT and PEP are believed to be the most suitable test for immediated clinical diagnosis.     

Physiologic modulations of the systolic time intervals in the fetal lamb

To examine the modulation of fetal systolic time intervals of the ovine fetus in relation to fetal maturation, heart rate, respiratory activity, and circadian rhythm, studies were carried out on 13 fetal-maternal sheep preparations. The data obtained showed that there was a significant correlation between the ejection time (ET) and the RR intervals of the electrocardiogram. The pre-ejection period (PEP) and PEP/ET increased in relation to the fetal maturation (38 ms and 0.25 at 120 days to 52 ms and 0.33 at 145 days of gestation, respectively). When the circadian rhythmicity was analyzed, a relative tachycardia was in evidence during the 21- to 03-h period but systolic time intervals remained unchanged. Except for some tachycardia and cardiac rhythm variability, respiratory activity also had no influence on the systolic time intervals.     

Earlier responses in the delay of Korotkoff sounds as compared to the Achilles reflex time in rapid changes of thyroid function in man.

In rapidly changing thyroid state Rodbard's Q-Kd interval (reflecting heart contractility) changes more rapidly, than ART (reflecting skeletal muscle contractility). After withdrawal of substitutive therapy in athyreotic patients the Q-Kd intervals prolongs more rapidly than ART and during intensive treatment of hypothyroidism the Q-Kd interval shortens more rapidly that ART. A more rapid metabolic turnover in heart muscle in comparison with skeletal muscle is proposed as suitable explanation. Practical consequences for early diagnosis of hypothyroidism and for instant functional diagnosis of thyroidal disorders are stressed.     

Adaptation of the circulatory system to frequently repeated submaximal workloads in the light of left ventricular contraction analysis

In two groups of healthy men aged 20-22 years the left ventricular systolic time intervals were evaluated by the method of Weissler et al. during frequently repeated workloads and restitution. Each exercise was carried out on a Zimmerman cycle ergometer during 10 minutes, and was repeated five times at 50-minutes intervals from 8.00 o'clock a.m. Group I (15 subjects) performed the exercise at a stable workload which produced during the first exercise heart rate acceleration to 170/min, but gave a successive further rise in the heart rate during consecutive exercises. Group II (11 subjects) performed all exercises to a stable rise in heart rate to 170/min with decreasing workloads. It was found that successive exercises caused in both groups a similar decrease of the left ventricular ejection time index (LVETI), pre-ejection period (PEP), isovolumetric contraction time (ICT), and decrease of the PEP/LVET index (p less than 0.05). Each successive exercise began with higher values of LVETI, PEP, ICT and PEP/LVET than the first one. No significant differences were found in the values of left ventricular systolic time intervals in both groups (p greater than 0.05). The duration of restitution of normal values of the left ventricular systolic time intervals after successive exercises was not changing but the tolerance of these exercises measured by heart rate increase and work performed decreased successively.     

Time intervals and patient-level factors in oral cancer diagnostic pathways: An application of the WHO framework in India

BackgroundOral cancer, a leading cancer-site in India, is often detected at advanced stages. We evaluated the time intervals from first symptom to help-seeking and diagnosis among oral cancer patients.MethodologyIn this cross-sectional study, we recruited 226 consecutive oral cancer patients (mean age ( ± SD) 51.9 years ( ± 10.9); 81.9% men; 70.3% advanced stage) registered for diagnosis and treatment, between 2019 and 2021 at a cancer care centre in South India. We used WHO framework and previously standardized tools to record time intervals (appraisal, help-seeking and diagnostic) and baseline characteristics. We utilized multivariable logistic regression models to test the associations between ‘prolonged (i.e., over 1 month) time intervals’) and patient-level factors to estimate odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOver a half of patients presented with prolonged appraisal (60%) and help-seeking intervals (57%), and a third (34%) reported prolonged diagnostic interval. Patients with no formal education, no routine healthcare visits, no self-reported risk factors, and those who did not perceive initial symptoms to be serious were 2–4 times more likely to have prolonged appraisal and help-seeking than the rest. High travel costs and self-decision for visiting healthcare facility prolonged help-seeking. Diagnostic interval was prolonged only among women OR= 2.7 (95% CI: 1.2–6.1)) and in patients whose first doctor’s opinion was ‘nothing to worry’ OR (=7.3 (95% CI: 2.6–20.5)). ‘Correct knowledge of cancer’ shortened appraisal and help-seeking intervals and ‘incorrect knowledge and negative beliefs’ prolonged diagnostic interval.ConclusionOur findings highlight that interventions targeting sociocultural and economic determinants, symptom awareness, sensitizing persons at risk (especially women) and primary care providers might reduce overall time to diagnosis. Further, patients without any known risk factors for oral cancer might be at-risk for prolonged appraisal interval. These might help inform ‘pull’ strategies for cancer control in India and similar settings.     

Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis".

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.     

The respiratory change in preejection period: a new method to predict fluid responsiveness.

The accuracy and clinical utility of preload indexes as bedside indicators of fluid responsiveness in patients after cardiac surgery is controversial. This study evaluates whether respiratory changes (Delta) in the preejection period (PEP; DeltaPEP) predict fluid responsiveness in mechanically ventilated patients. Sixteen postcoronary artery bypass surgery patients, deeply sedated under mechanical ventilation, were enrolled. PEP was defined as the time interval between the beginning of the Q wave on the electrocardiogram and the upstroke of the radial arterial pressure. DeltaPEP (%) was defined as the difference between expiratory and inspiratory PEP measured over one respiratory cycle. We also measured cardiac output, stroke volume index, right atrial pressure, pulmonary arterial occlusion pressure, respiratory change in pulse pressure, systolic pressure variation, and the Deltadown component of SPV. Data were measured without positive end-expiratory pressure (PEEP) and after application of a PEEP of 10 cmH2O (PEEP10). When PEEP10 induced a decrease of >15% in mean arterial pressure value, then measurements were re-performed before and after volume expansion. Volume loading was done in eight patients. Right atrial pressure and pulmonary arterial occlusion pressure before volume expansion did not correlate with the change in stroke volume index after the fluid challenge. Systolic pressure variation, DeltaPEP, Deltadown, and change in pulse pressure before volume expansion correlated with stroke volume index change after fluid challenge (r2 = 0.52, 0.57, 0.68, and 0.83, respectively). In deeply sedated, mechanically ventilated patients after cardiac surgery, DeltaPEP, a new method, can be used to predict fluid responsiveness and hemodynamic response to PEEP10.     

Lingual thyroid: a rare disease resembling base of tongue neoplasm

The ectopic thyroid gland occurring in the midline of the base of tongue is a rare developmental anomaly. It may cause differential diagnostic problems with real malignant tumor. Symptoms, if where are any: foreign-body-feeling, swallowing difficulties, dyspnea, articulation disorders, bleeding and hypothyroidism, but in many cases the diagnosis is accidental. We describe two cases of lingual thyroid gland operated in our department, and discuss the present trends of the treatment of this disease. We agree with most of the authors that only cases presenting with symptoms should be operated, and if possible the normal thyroid tissue should be replaced into the body. However, all discovered cases have to be followed to avoid late hormonal disturbances.     

Fetal gender determination and BclI polymorphism using nucleated erythrocytes in maternal blood.

This study demonstrated determination of fetal gender from nucleated red blood cells (NRBCs) in maternal blood and attempted to apply prenatal diagnosis of hemophilia A using BclI DNA polymorphism. Venous blood was drawn from 20 pregnant women, and NRBCs were recovered by magnetic activated cell sorting and anti-GPA (glycophorin A) immunostaining. After microdissector isolation of the NRBCs, primer extension preamplification (PEP) and nested PCR of the amelogenin gene were performed to determine fetal gender. We also performed PEP and nested PCR of BclI polymorphism to verify the validity of prenatal diagnosis of hemophilia A. DNA amplification was achieved in 107 cells (51.9%) and fetal gender determined with 65.0% accuracy. Unfortunately, we could not verify the validity within the scope of this study. However, in a larger number of cases that are informative in BclI polymorphism, we will be able to identify patients affected by hemophilia A using fetal NRBCs in maternal blood.     

Dynamics of changes in the cardiovascular response to submaximal exercise during low-intensity endurance training with particular reference to the systolic time intervals

Eighteen male volunteers (aged 20-23 years), not involved in any sporting activities, were submitted to 13 weeks of training consisting of 30 min exercise [at 50%-75% maximal oxygen intake (VO2max)] on a cycle ergometer, performed 3 times a week. Every 4 weeks cardiac function was evaluated by measuring the systolic time intervals at rest and during submaximal cycle exercise. Stroke volume (SV), heart rate (HR) and blood pressure (BP) responses to submaximal exercise, VO2max and anaerobic threshold (AT) were also determined. Significant increases in VO2max, increases in AT and SV at the submaximal exercise intensities, as well as decreases in HR and BP were found after 4 weeks of training. Resting systolic time intervals were not affected by training, but during the submaximal cycle exercise the values of the pre-ejection period (PEP) and isovolumic contraction time (ICT) corresponding to HR of 100 beats.min-1 were significantly lowered after 13 weeks of training, whereas PEP, ICT and total electromechanical systole corresponding to HR of 130 beats.min-1 were significantly shortened by the 4th week. The ratios of PEP:LVET (left ventricular ejection time) and ICT:LVET during submaximal exercise were significantly lowered by training starting from the 8th week. These changes might be interpreted as evidence of the training-induced enhancement of the "contractility reserve", i.e. the ability to increase heart muscle contractility with increasing exercise intensity.     

Amblyomma americanum (L): Tick macrophage migration inhibitory factor peptide immunization lengthens lone star tick feeding intervals in vivo

Immunizations of New Zealand White rabbits with specific macrophage migration inhibitory factor (MIF) tick peptide (PEP) produced circulating anti-tick PEP antibodies in the hosts. Antibody titers of greater than 1:5000 to tick MIF peptide were observed for crude sera from PEP-immunized rabbits. PEP- and BSA-vaccinated rabbits were infested with Amblyomma americanum adults. Feeding intervals, female weights, egg masses and percent egg hatch were measured for ticks feeding on control and immunized hosts. Feeding intervals were significantly lengthened to 13.3 days for PEP-vaccinated hosts compared to BSA-vaccinated controls at 12.4 days, while female engorgement weights and egg masses were unchanged. By immunizing hosts using specific tick PEP, we were able to alter the length of time the ticks fed on their hosts.     

Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection.     

Time intervals from first symptom to diagnosis for head and neck cancers: An analysis of linked patient reports and medical records from the UK

BackgroundEngland has significantly higher mortality risks due to Head and Neck Cancer (HNC) compared with other European countries. Early diagnosis is important as it is likely to increase early-stage diagnosis and improve survival and better quality of life. This study sought to improve understanding of the intervals from first symptom recognition to diagnosis for HNC and investigate associations between patient-reported symptoms and socio-demographic factors.MethodsPeople within 3 months of diagnosis, completed a researcher-administered questionnaire and data were extracted from primary and secondary care clinical records.ResultsEighty (mean age 62.9 [SD 11.7] years; 66% men) were interviewed. The appraisal interval was longer than a month for 39% of participants and the help-seeking interval was longer than a week for 44%. The median diagnostic interval was 92 (IQR; 34-172) days. Appraisal intervals of > 1 month were associated with male gender, ulceration and persistent throat pain. The only symptom that associated with a help-seeking interval of > 1 week was ulceration. Participants who reported red/white patches in the mouth and ulceration were associated with a reduced likelihood of a diagnostic interval of > 3 months. A higher proportion of participants with a diagnostic interval of > 3 months were diagnosed with advanced disease (78%) than those with an interval < 3 months (68%).ConclusionThese data improve understanding of the intervals from first symptom recognition to HNC diagnosis and provide preliminary evidence to identify targets to reduce overall time to diagnosis.     

Timing of repeat thyroid fine-needle aspiration in the management of thyroid nodules

Objective: The Bethesda System for reporting thyroid fine-needle aspirations (FNAs) recommends repeat aspirations be done at least 3 months following the initial aspiration to prevent false-positive misinterpretations due to reactive/reparative changes. Because limited data exists, we reviewed our own data to ascertain the recommendation. Study Design: We retrospectively reviewed thyroid FNAs accessioned in the Cytology Laboratory at Beth Israel Deaconess Medical Center in Boston, Mass., USA, from January 2006 to December 2008. We identified patients with repeat aspirates of a single lesion and those with thyroidectomy specimens. Cytologic and surgical diagnoses along with time between FNAs were recorded. Results: No statistically significant difference was detected in the distribution among nondiagnostic, suboptimal, and adequate categories with respect to the timing of repeat FNA (p = 0.25). Forty-six percent of the lesions that were nondiagnostic/suboptimal initially yielded the same results on repeat. Twenty-eight percent of initially adequate specimens were nondiagnostic/suboptimal on repeat (p = 0.04). Nine percent of those with an initial atypical diagnosis had the same diagnosis on repeat, while 2.6% of those who did not have an initial atypical diagnosis had an atypical diagnosis on repeat (p = 0.29). False positives between early (16%) and late (12%) repeats were not statistically significant (p = 0.74). Conclusion: The diagnostic yield and accuracy of repeat FNA is independent of the time interval between procedures but may be related to the original FNA diagnosis.     

Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.     

Effect of static exercise and muscle ischemia on cardiac function as evaluated by the systolic time intervals

To determine the role of muscle chemoreflex in the cardiac response to static exercise the effect of the forearm muscle ischemia on systolic time intervals (STI), heart rate (HR) and blood pressure (BP) recovery following static handgrip was studied in 7 healthy men. During handgrip maintained for 4 min at 30% maximal voluntary contraction HR and BP increased significantly while duration of the pre-ejection period (PEP) and isovolumic contraction time (ICT) were shortened with a significant lowering in the ratio of PEP to the left ventricle ejection time (LVET). Occlusion of the circulation to the forearm muscles for 2 min after cessation of exercise did not prevent a rapid decline of HR or increment in PEP, ICT and PEP-to-LVET ratio while BP remained elevated for as long as blood flow to muscles was restricted. The study failed to demonstrate an appreciable effect of muscle chemoreflex on HR or myocardial contractility, suggesting that input from muscle afferents activated by metabolic stimuli induces the pressor response mainly by the peripheral vasoconstriction.     

Confirming the diagnosis of mild hypertension.

Patients with newly found raised blood pressure are known to have lower pressures at subsequent measurements even when not treated. A study was undertaken to determine the extent to which (a) the number of follow-up measurements and (b) the duration of the intervals between them contributed to this fall in pressure. In 42 general practices 110 patients were identified as having for the first time a diastolic pressure (phase V) greater than 90 and less than 110 mm Hg. Both diastolic and systolic pressures were appreciably lower when measured at return visits when compared with the first measurement. The systolic pressure dropped appreciably in the intervals between the first and the second visits and again between the second and third visits. The diastolic pressure fell appreciably only between the first and second visits. The duration of the interval between visits was not associated with a fall in either systolic or diastolic pressure, but the number of measurements was. This pattern of fall in pressure was not affected by the patient''s age or sex. From these results we conclude that patients with newly identified blood pressures that are mildly raised should be seen at two further visits before a decision about treatment is made. The timing of these follow-up visits is not crucial.     

甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值分析

目的:研究甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值。方法:选取从2016年3月~2019年2月于我院接受手术治疗的甲状腺疾病患者300例作为研究对象,均予以彩超检查,比较甲状腺良恶性结节的超声特征(主要包括直径、钙化情况、边界、回声、血流状况)。以病理活检结果为金标准,分析彩超诊断甲状腺结节良恶性的敏感性、特异性以及准确度。对比甲状腺良恶性结节的血流分型情况以及各项血流动力学参数。结果:恶性结节超声特征直径≥2 cm、有钙化、边界模糊、无回声/低回声、血流丰富人数占比均高于良性结节(均P<0.05)。以手术病理组织活检结果作为金标准,彩色多普勒超声诊断甲状腺结节的敏感性、特异性以及准确度分别为97.73%、86.11%、96.33%。甲状腺良性结节血流分型为Ⅰ型、Ⅱ型人数占比高于恶性结节,而Ⅲ型、Ⅳ型人数占比低于恶性结节(均P<0.05)。甲状腺良性结节的收缩期峰值血流速度(PSV)、阻力指数(RI)均低于恶性结节,而舒张末期血流速度(EDV)高于恶性结节(均P<0.05)。结论:彩色多普勒超声对甲状腺结节良恶性的鉴别价值较高,且具有较高的敏感性、特异性以及准确度,可为甲状腺良恶性结节的早期诊断、临床治疗提供重要的参考依据。     

Natriuretic peptides: their role in diagnosis and therapy

Cardiac natriuretic peptide hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are synthesized and secreted by the heart, producing several biological effects, such as natriuresis, vasorelaxation and hypotension. During the last decade these peptides, especially BNP, have received increasing attention as potential markers of cardiovascular disease. Their measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money. BNP levels can enable the differentiation between dyspnoic patients secondary to ventricular dysfunction and subjects with primary respiratory disorders. Moreover, there is good evidence that natriuretic peptides may have a diagnostic role in arterial hypertension, acute coronary syndromes, pulmonary hypertension, some valvular heart disease and some disorders affecting other systems (diabetes or thyroid disorders). In this paper we discuss the clinical utility of assessment of natriuretic peptide hormones in the diagnosis of various clinical conditions and their use as pharmacological agents.     

Hyperthyroidism in the elderly: aspecific signs may cause a delay in diagnosis

The clinical manifestations of thyroid diseases in the elderly are often atypical and can easily be attributed to other medical conditions or 'normal aging'. Two nursing home patients with hyperthyroidism are described. Due to the atypical presentation of the thyroid disease their complaints were attributed to other conditions. In both patients there was a significant delay in diagnosis and treatment of hyperthyroidism. In elder patients signs and symptoms of thyreotoxicosis are frequently related to cardiovascular, gastrointestinal and neuropsychiatric disorders. Most often occur atrial fibrillation, worsening of cardiac failure and angina pectoris, weight loss, anorexia, constipation, cognitive impairment and delirium. Delay of diagnosis and treatment of hyperthyroidism may be potentially harmful to the patient. Untreated thyreotoxicosis may lead to serious cardiovasculair complications (particularly cardiac failure and cerebrovascular accidents), mental deterioration and osteoporosis. In elder people with unexplained and vague signs and symptoms thyroid function should always be checked. The TSH assay is a very accurate diagnostic test for screening thyroid function. A normal TSH indicates euthyroidism with an accuracy of almost 100%. The medical treatment for hyperthyreoidism in the elderly are antithyroid drugs. When an euthyroid state is rendered, suppletion with L-thyroxine may be nessecary. Radioactive iodine treatment is preferred in some cases though there may be practical difficulties with the application of this treatment in nursing home patients because temporary isolation is necessary.